Pneumococcal pneumonia in adults – Re-emergence of vaccine serotypes: a prospective multicentre cohort study in Germany, 2020-2023

  1. Christina Bahrs
  2. Norman Rose
  3. Grit Barten-Neiner
  4. Carolin Fleischmann-Struzek
  5. Mark P. G. van der Linden
  6. Gernot Rohde
  7. Jan Rupp
  8. Martin Witzenrath
  9. Jessica Rademacher
  10. Mathias W. Pletz

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Abstract

This prospective multicentre study investigated pneumococcal serotype distribution and vaccine coverage of the 13- and 20-valent conjugate vaccines, and the 23-valent polysaccharide vaccine among adults with community-acquired pneumonia in Germany, from 2020 to 2023, using serotype-specific urine antigen detection testing. The findings show that Streptococcus pneumoniae has reemerged as causative pathogen of pneumonia, particularly in adults aged ≥60 years. This resurgence, observed during the ongoing SARS-CoV-2 pandemic, has been primarily driven by an increase in cases due to serotype 3.

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  1. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/17719974.

    Summary/Abstract:

    • This preprint analyzes a multicentre study investigating pneumococcal serotype distribution and vaccine coverage of several vaccines. 

    • The administration of these vaccines focused on adults with community-acquired pneumonia in Germany, from 2020 to 2023, using serotype specific urine antigen detection testing.  The tests include BINAX NOW, Blood Culture, SSAUD, and detection of PCV13 serotypes by several other tests (grouped testing).   

    • The findings showed that Streptococcus pneumoniae has reemerged as a causative agent of pneumonia, particularly found in adults aged 60 years or older.  This resurgence was observed during the SARS COV 2 pandemic, and driven by a specific serotype named by the authors (Serotype 3).

    Overall Impression & Recommendations

    This preprint addresses an important clinical question to determine the pneumococcal serotype re-emergence in adults, but requires strong methodological strengthening to determine a statistically significant re-emergence.  The three detection methods (SSAUD, Binax NOW, and blood culture) did not show significant results for significant re-emergence either. For example, the study demonstrates no identifiable vaccine serotype in 33% of blood culture serotypes.  

    • I would recommend that the authors reevaluate the framing of their study, considering the confounding variables of the pandemic, which the authors do acknowledge.  Using 2020 as a baseline for all infections is a problematic statement since efforts to mitigate the pandemic were already present (face masks, vaccines), and using artificially low starting points of inflection in infection could inflate statistical data.

    An understanding of an appropriate control for when changes in healthcare can affect utilization of the vaccine tests at home, diagnostic practices in clinical settings, and causal inferences about a true epidemiological "re-emergence" versus recovery artifacts from healthcare system disruption.

    Methods

    The most concerning finding between the three diagnostic methods (SSAUD, Binax NOW, and blood culture) is that there is no comprehensive statistical analysis or control between the three to establish reliability.  There were substantial differences in data between the three, with detection rates as follows (SSAUD - 8.7%, BinaxNOW - 5.13%, blood culture - 2.42%) which indicates systemic sensitivity differences. 

    • This could introduce significant biases in epidemiological conclusions. Most concerning is the finding that 33.33% (8/24) of culture-confirmed bacteremic pneumococcal cases demonstrated no identifiable vaccine serotype coverage. Data demonstrate a 71% high detection rate from SSAUD compared to BinaxNOW. This confirms that these tests have different sensitivities for specific serotypes or disease presentations, but no analysis is done to determine which serotype is preferentially detected by each method or why there are such substantial differences between them. (Table 1 information cited here).

    Results

    The study demonstrated that there were data missing from 524/1,504 patients (35.84%) who have all not used SSUAD Testing. 

    • There may be a conflict of interest with Pfizer (unsure) as Pfizer is responsible for the funding of this study, and therefore, may want to characterize positive results of the SSUAD test.  To supplement, the authors provide no characterization of whether these exclusions would represent missing information, which would then create potential for systematic bias in serotype distribution estimates.  

    • A baseline solution would be characterizing the missing SSUAD data and blood culture data by patient demographics, clinical severity scores, hospital site, and the study years to assess missing data mechanisms. There should be sensitivity analyses which would compare the complete-case results with the imputed data sets to assess the robustness of the trend estimates.  

    • Testing whether missingness patterns change significantly over the study period using a logistic regression model will promote efficacy of the study.  Reporting any missing data and discussing the implications of generalizing the study will also promote its efficacy.  

    References

    References seem cited appropriately.  A mix of broad pandemic data analyzed with research on statistical modeling methods, the diagnostic tests, and the re-emergence cases of pneumococcal pneumonia in past years.

    Competing interests

    The author declares that they have no competing interests.

    Use of Artificial Intelligence (AI)

    The author declares that they did not use generative AI to come up with new ideas for their review.

  2. Version published to 10.1101/2025.10.24.25338303 on medRxiv